The purpose of the present thesis was to examine and quantitatively study key postnatal events in the developing and mature human cerebral cortex within the context of the systematic variation in the laminar structure of the cortex that underlies connectivity patterns and cortical function. To address this, we expanded upon previous work completed by LeRoy Conel and performed extensive analysis of Cresyl-Violet, Cajal, and Golgi-Cox images of various Von-Economo’s Areas for five age groups in order to see where variations in dendritic tree arborization, which is visualized by Golgi-Cox staining, pruning, which is visualized by Cresyl Violet staining, and cytoskeletal changes, which are visualized by Cajal staining, may lie. The results of this analysis showed that across all age groups and cortical types, there are consistently high levels of dendritic tree arborization, cytoskeletal changes, and cell body density changes in all layers across younger age groups, followed by slight declines in older age groups, following the trend of rapid gray matter expansion during the first two years of postnatal life before shifting towards white matter growth. These levels were also the most exaggerated in cortical layers III and V of Agranular, Dysgranular, Eulaminate II, and Eulaminate III areas, suggesting that cortical layers III and V of these areas change the most rapidly during the key events of postnatal development that Conel sought to analyze in his staining experiments. We also found that in layers III and V, Golgi-Cox values increased, reflecting the growth of dendritic trees while Cresyl-Violet and Cajal values decreased, reflecting decreases in cell body density, allowing for increased space between cells, highlighting a complementary inverse relationship that is seen between neurite outgrowth and cell body density. Since postnatal developmental processes in the cortex are largely driven by transcription factors that regulate chromatin expression well into adulthood, we also examined how certain epigenetic modifications in the nuclei of neurons in the adult cortex may explain for variations seen between areas in the analysis of Conel’s images. To address this, we analyzed populations of H4K12 and SC35 expressing pyramidal neurons in layers III and V of Area 46 and Area 32 in order to further understand how patterns of acetylation and RNA splicing may play a role in the rapid changes of layers III and V seen in Eulaminate II and Dysgranular areas. In the case of SC35, higher levels of splicing were seen in layer III of Area 32 and layer V of Area 46, suggesting that splicing centers within the neurons of these layers and areas are more organized. In the case of H4K12, similar levels of acetylation were observed in layers III and V of Area 46 whereas higher levels were observed in layer V of Area 32, indicating a certain degree of regulation of gene expression within these areas. The results of this study demonstrate variations in the timing of the major events of postnatal development across layers in different structural types of cortical areas that correspond to limbic, multimodal, and highly specialized unimodal areas and the inverse relationship seen between neurite outgrowth and changes in cell body density. Additionally, these results demonstrate the impact that patterns of RNA splicing and acetylation may have on these events and can be utilized to identify disruptions in developmental disorders such as autism. / 2024-09-21T00:00:00Z

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